Advanced search
Publication Cover
Xenobiotica
the fate of foreign compounds in biological systems
Volume 38, 2008 - Issue 6
Submit an article Journal homepage
472
Views
57
CrossRef citations to date
0
Altmetric
Original Articles

Pre-clinical pharmacokinetics of UK-453,061, a novel non-nucleoside reverse transcriptase inhibitor (NNRTI), and use of in silico physiologically based prediction tools to predict the oral pharmacokinetics of UK-453,061 in man

G. Allan Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
,
J. Davis Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
,
M. Dickins Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
,
I. Gardner Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
,
T. Jenkins Clinical Research, Pfizer Global Research and Development , Sandwich, UK
,
H. Jones Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
,
R. Webster Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
&
H. Westgate Clinical Pharmacology, Pharmacokinetics, Dynamics and Metabolism , Sandwich, UK
 show all
Pages 620-640 | Received 15 Feb 2008, Accepted 19 Mar 2008, Published online: 22 Sep 2008

Citations (57)

Keep up to date with the latest research on this topic with citation updates for this article.

Subscribe to citation updates

Read on this site (10)

Amit S. Kalgutkar, Kosea S. Frederick, Heather L. Hatch, Catherine M. Ambler, David A. Perry, Ravi S. Garigipati, George C. Chang, Bruce A. Lefker, Ronald W. Clark, Lee A. Morehouse, Omar Francone & Xiao Hu. (2014) Identification of a novel, non-tetrahydroquinoline variant of the cholesteryl ester transfer protein (CETP) inhibitor torcetrapib, with improved aqueous solubility. Xenobiotica 44:7, pages 591-605.
Read now
Martin Platten & Gerd Fätkenheuer. (2013) Lersivirine – a new drug for HIV infection therapy. Expert Opinion on Investigational Drugs 22:12, pages 1687-1694.
Read now
Hannah M Jones, Maurice Dickins, Kuresh Youdim, James R Gosset, Neil J Attkins, Tanya L Hay, Ian K Gurrell, Y Raj Logan, Peter J Bungay, Barry C Jones & Iain B Gardner. (2012) Application of PBPK modelling in drug discovery and development at Pfizer. Xenobiotica 42:1, pages 94-106.
Read now
Jennifer B Dressman, Kirstin Thelen & Stefan Willmann. (2011) An update on computational oral absorption simulation. Expert Opinion on Drug Metabolism & Toxicology 7:11, pages 1345-1364.
Read now
Angus N.R. Nedderman, Gordon J. Dear, Stephanie North, R. Scott Obach & David Higton. (2011) From definition to implementation: a cross-industry perspective of past, current and future MIST strategies. Xenobiotica 41:8, pages 605-622.
Read now
Andrea N Edginton & Ghanashyam Joshi. (2011) Have physiologically-based pharmacokinetic models delivered?. Expert Opinion on Drug Metabolism & Toxicology 7:8, pages 929-934.
Read now
K.S. Frederick, T.S. Maurer, A.S. Kalgutkar, L.J. Royer, O.L. Francone, S.M. Winter, S.G. Terra, D. Chen & X. Gao. (2009) Pharmacokinetics, disposition and lipid-modulating activity of 5-{2-[4-(3,4-difluorophenoxy)-phenyl]-ethylsulfamoyl}-2-methyl-benzoic acid, a potent and subtype-selective peroxisome proliferator-activated receptor α agonist in preclinical species and human. Xenobiotica 39:10, pages 766-781.
Read now
C. R. Gibson, A. Bergman, P. Lu, F. Kesisoglou, W. S. Denney & E. Mulrooney. (2009) Prediction of Phase I single-dose pharmacokinetics using recombinant cytochromes P450 and physiologically based modelling. Xenobiotica 39:9, pages 637-648.
Read now
D. K. Walker, J. Davis, C. Houle, I. B. Gardner & R. Webster. (2009) Species differences in the multiple-dose pharmacokinetics of the non-nucleoside reverse transcriptase inhibitor (NNRTI) UK-453,061 in animals and man: implications for safety considerations. Xenobiotica 39:7, pages 534-543.
Read now
Masoud Jamei, Steve Marciniak, Kairui Feng, Adrian Barnett, Geoffrey Tucker & Amin Rostami-Hodjegan. (2009) The Simcyp® Population-based ADME Simulator. Expert Opinion on Drug Metabolism & Toxicology 5:2, pages 211-223.
Read now

Articles from other publishers (47)

Hunter D. J. Webb, David B. Finlay, Shuli Chen, Andrea J. Vernall, Eric Sparkes, Samuel D. Banister, Rhonda J. Rosengren & Michelle Glass. (2022) Characterisation of AMB-FUBINACA metabolism and CB1-mediated activity of its acid metabolite. Forensic Toxicology 41:1, pages 114-125.
Crossref
Yue Pan. 2021. The Medicinal Chemist's Guide to Solving ADMET Challenges. The Medicinal Chemist's Guide to Solving ADMET Challenges 278 302 .
Bret BernerRichard N. Upton, Ashley M. Hopkins, Ahmad Y. Abuhelwa, Jim H. Hughes & David J.R. Foster. 2021. Drug Delivery Approaches. Drug Delivery Approaches 43 73 .
Bret BernerToufigh Gordi & Bret Berner. 2021. Drug Delivery Approaches. Drug Delivery Approaches 1 41 .
Byeong ill LeeJeong-hyeon LimMin-Ho ParkSeok-Ho ShinJin-Ju ByeonJang-mi ChoiSeo-jin ParkMin-jae ParkYuri ParkYoung G. Shin. (2020) Qualification and application of liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of carisbamate in rat plasma and prediction of its human pharmacokinetics using physiologically based pharmacokinetic modeling. Translational and Clinical Pharmacology 28:3, pages 147.
Crossref
Byeong ill Lee, Min-Ho Park, Seok-Ho Shin, Jin-Ju Byeon, Yuri Park, Nahye Kim, Jangmi Choi & Young G. Shin. (2019) Quantitative Analysis of Tozadenant Using Liquid Chromatography-Mass Spectrometric Method in Rat Plasma and Its Human Pharmacokinetics Prediction Using Physiologically Based Pharmacokinetic Modeling. Molecules 24:7, pages 1295.
Crossref
Hidetoshi Shimizu, Kosuke Yoshida, Tomohisa Nakada, Koki Kojima, Akihito Ogasawara, Yoshinobu Nakamaru & Hiroshi Yamazaki. (2019) Prediction of Human Distribution Volumes of Compounds in Various Elimination Phases Using Physiologically Based Pharmacokinetic Modeling and Experimental Pharmacokinetics in Animals. Drug Metabolism and Disposition 47:2, pages 114-123.
Crossref
Eman Alraddadi, Ryan Lillico, Jonathan Vennerstrom, Ted Lakowski & Donald Miller. (2018) Absolute Oral Bioavailability of Creatine Monohydrate in Rats: Debunking a Myth. Pharmaceutics 10:1, pages 31.
Crossref
Fen Yang, Baolian Wang, Zhihao Liu, Xuejun Xia, Weijun Wang, Dali Yin, Li Sheng & Yan Li. (2017) Prediction of a Therapeutic Dose for Buagafuran, a Potent Anxiolytic Agent by Physiologically Based Pharmacokinetic/Pharmacodynamic Modeling Starting from Pharmacokinetics in Rats and Human. Frontiers in Pharmacology 8.
Crossref
Ayman F. El‐Kattan. 2017. Oral Bioavailability Assessment. Oral Bioavailability Assessment 347 355 .
Deepak K. Dalvie, R. Scott Obach & Amit S. Kalgutkar. 2016. Metabolite Safety in Drug Development. Metabolite Safety in Drug Development 261 273 .
Hannah M. Jones, Richard P. Butt, Rob W. Webster, Ian Gurrell, Pawel Dzygiel, Neil Flanagan, Daniela Fraier, Tanya Hay, Laura Else Iavarone, Jacquelynn Luckwell, Hannah Pearce, Alex Phipps, Jill Segelbacher, Bill Speed & Kevin Beaumont. (2016) Clinical Micro-Dose Studies to Explore the Human Pharmacokinetics of Four Selective Inhibitors of Human Nav1.7 Voltage-Dependent Sodium Channels. Clinical Pharmacokinetics 55:7, pages 875-887.
Crossref
Ioannis P. Androulakis. (2016) Quantitative Systems Pharmacology: A Framework for Context. Current Pharmacology Reports 2:3, pages 152-160.
Crossref
D. C. Pryde, B. Marron, C. G. West, S. Reister, G. Amato, K. Yoger, K. Padilla, J. Turner, N. A. Swain, P. J. Cox, S. E. Skerratt, T. Ryckmans, D. C. Blakemore, J. Warmus & A. C. Gerlach. (2016) The discovery of a potent series of carboxamide TRPA1 antagonists. MedChemComm 7:11, pages 2145-2158.
Crossref
Jan F. Schlender, Adam G. Golden, Tanay S. Samant, Chakradhar V. Lagishetty & Stephan Schmidt. 2016. Developing Drug Products in an Aging Society. Developing Drug Products in an Aging Society 589 611 .
Zhi-wei Gao, Yun-ting Zhu, Ming-ming Yu, Bin Zan, Jia Liu, Yi-fan Zhang, Xiao-yan Chen, Xue-ning Li & Da-fang Zhong. (2015) Preclinical pharmacokinetics of TPN729MA, a novel PDE5 inhibitor, and prediction of its human pharmacokinetics using a PBPK model. Acta Pharmacologica Sinica 36:12, pages 1528-1536.
Crossref
Baolian Wang, Zhihao Liu, Dan Li, Shuang Yang, Jinping Hu, Hui Chen, Li Sheng & Yan Li. (2015) Application of physiologically based pharmacokinetic modeling in the prediction of pharmacokinetics of bicyclol controlled-release formulation in human. European Journal of Pharmaceutical Sciences 77, pages 265-272.
Crossref
Mark D. Andrews, Kerry af Forselles, Kevin Beaumont, Sébastien R. G. Galan, Paul A. Glossop, Mathilde Grenie, Alan Jessiman, Amy S. Kenyon, Graham Lunn, Graham Maw, Robert M. Owen, David C. Pryde, Dannielle Roberts & Thien Duc Tran. (2015) Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain. ACS Medicinal Chemistry Letters 6:4, pages 419-424.
Crossref
Florian Wakenhut, Thien Duc Tran, Chris Pickford, Stephen Shaw, Mike Westby, Caroline Smith-Burchnell, Lesa Watson, Michael Paradowski, Jared Milbank, David Stonehouse, Kathy Cheung, Robert Wybrow, Felice Daverio, Samuel Crook, Keith Statham, David Leese, Darren Stead, Fiona Adam, Duncan Hay, Lee R. Roberts, Jean-Yves Chiva, Carly Nichols, David C. Blakemore, Gilles H. Goetz, Ye Che, Iain Gardner, Satish Dayal, Andrew Pike, Rob Webster & David C. Pryde. (2014) The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile-Part 2. ChemMedChem 9:7, pages 1387-1396.
Crossref
Thien Duc Tran, Florian Wakenhut, Chris Pickford, Stephen Shaw, Mike Westby, Caroline Smith-Burchnell, Lesa Watson, Michael Paradowski, Jared Milbank, Rebecca A. Brimage, Rebecca Halstead, Rebecca Glen, Craig P. Wilson, Fiona Adam, Duncan Hay, Jean-Yves Chiva, Carly Nichols, David C. Blakemore, Iain Gardner, Satish Dayal, Andrew Pike, Rob Webster & David C. Pryde. (2014) The Discovery of Potent Nonstructural Protein 5A (NS5A) Inhibitors with a Unique Resistance Profile-Part 1. ChemMedChem 9:7, pages 1378-1386.
Crossref
Hannah M. Jones & Neil Parrott. 2014. Predictive ADMET. Predictive ADMET 167 188 .
Masoud Jamei, Karen Yeo & Amin Rostami-Hodjegan. 2014. Handbook of Personalized Medicine. Handbook of Personalized Medicine 685 726 .
Marco SiccardiRajith Kumar Reddy Rajoli, Paul Curley, Adeniyi Olagunju, Darren Moss & Andrew Owen. (2013) Physiologically based pharmacokinetic models for the optimization of antiretroviral therapy: recent progress and future perspective. Future Virology 8:9, pages 871-890.
Crossref
Hannah M. Jones, Kapil Mayawala & Patrick Poulin. (2012) Dose Selection Based on Physiologically Based Pharmacokinetic (PBPK) Approaches. The AAPS Journal 15:2, pages 377-387.
Crossref
David C. Pryde, Thien-Duc Tran, Iain Gardner, Helen Bright, Paul Stupple, Sebastien Galan, Liam Alsop, Lesa Watson, Donald S. Middleton, Satish Dayal, Michelle Platts, Edward J. Murray, Tanya Parkinson & Robert Webster. (2013) Non-benzimidazole containing inhibitors of respiratory syncytial virus. Bioorganic & Medicinal Chemistry Letters 23:3, pages 827-833.
Crossref
David C. Pryde, Thien-Duc Tran, Mark Gardner, Chris Pickford, Stephen M. Shaw, Mike Westby, Tanya Parkinson, Caroline Smith-Burchnell, Rob Webster & Satish Dayal. (2013) Identification of HCV Inhibitors from a Cell-Based Sub-Genomic Replicon Screen. Open Journal of Medicinal Chemistry 03:01, pages 16-25.
Crossref
David C. Pryde, Rob Webster, Scott L. Butler, Edward J. Murray, Kevin Whitby, Chris Pickford, Mike Westby, Michael J. Palmer, David J. Bull, Hannah Vuong, David C. Blakemore, Darren Stead, Christopher Ashcroft, Iain Gardner, Claire Bru, Wai-Yee Cheung, Ieuan O. Roberts, Jennifer Morton & Richard A. Bissell. (2013) Discovery of an HIV integrase inhibitor with an excellent resistance profile. MedChemComm 4:4, pages 709.
Crossref
Douglas K. Spracklin, Amit S. Kalgutkar & Angus N. R. Nedderman. 2014. Reducing Drug Attrition. Reducing Drug Attrition 97 137 .
Gregg D. Cappon, Christopher J. Bowman, Sarah N. Campion, Gary Chmielewski, Mark E. Hurtt, Gregory L. Finch & Elise M. Lewis. (2012) Developmental Toxicity Study of Lersivirine in Mice. Birth Defects Research Part B: Developmental and Reproductive Toxicology 95:3, pages 225-230.
Crossref
Hannah M. Jones, Hugh A. Barton, Yurong Lai, Yi-an Bi, Emi Kimoto, Sarah Kempshall, Sonya C. Tate, Ayman El-Kattan, J. Brian Houston, Aleksandra Galetin & Katherine S. Fenner. (2012) Mechanistic Pharmacokinetic Modeling for the Prediction of Transporter-Mediated Disposition in Humans from Sandwich Culture Human Hepatocyte Data. Drug Metabolism and Disposition 40:5, pages 1007-1017.
Crossref
David C. Pryde, Thien-Duc Tran, Peter Jones, Jonathan Duckworth, Martin Howard, Iain Gardner, Ruth Hyland, Rob Webster, Tracey Wenham, Sharan Bagal, Kiyoyuki Omoto, Richard P. Schneider & Jian Lin. (2012) Medicinal chemistry approaches to avoid aldehyde oxidase metabolism. Bioorganic & Medicinal Chemistry Letters 22:8, pages 2856-2860.
Crossref
Yuan Chen, Jin Y. Jin, Sophie Mukadam, Vikram Malhi & Jane R. Kenny. (2012) Application of IVIVE and PBPK modeling in prospective prediction of clinical pharmacokinetics: strategy and approach during the drug discovery phase with four case studies. Biopharmaceutics & Drug Disposition 33:2, pages 85-98.
Crossref
Christopher L. Shaffer, Renato J. Scialis, Haojing Rong & R. Scott Obach. (2012) Using Simcyp to project human oral pharmacokinetic variability in early drug research to mitigate mechanism-based adverse events. Biopharmaceutics & Drug Disposition 33:2, pages 72-84.
Crossref
Helen Small, Iain Gardner, Hannah M. Jones, John Davis & Malcolm Rowland. (2011) Measurement of Binding of Basic Drugs to Acidic Phospholipids Using Surface Plasmon Resonance and Incorporation of the Data into Mechanistic Tissue Composition Equations to Predict Steady-State Volume of Distribution. Drug Metabolism and Disposition 39:10, pages 1789-1793.
Crossref
Patrick Poulin, Rhys D.O. Jones, Hannah M. Jones, Christopher R. Gibson, Malcolm Rowland, Jenny Y. Chien, Barbara J. Ring, Kimberly K. Adkison, M. Sherry Ku, Handan He, Ragini Vuppugalla, Punit Marathe, Volker Fischer, Sandeep Dutta, Vikash K. Sinha, Thorir Björnsson, Thierry Lavé & James W.T. Yates. (2011) PHRMA CPCDC initiative on predictive models of human pharmacokinetics, part 5: Prediction of plasma concentration–time profiles in human by using the physiologically‐based pharmacokinetic modeling approach. Journal of Pharmaceutical Sciences 100:10, pages 4127-4157.
Crossref
Peter J. Bungay, Sarah Tweedy, David C. Howe, Karl R. Gibson, Hannah M. Jones & Natalie M. Mount. (2011) Preclinical and Clinical Pharmacokinetics of PF-02413873, a Nonsteroidal Progesterone Receptor Antagonist. Drug Metabolism and Disposition 39:8, pages 1396-1405.
Crossref
Lyn H. Jones, Gill Allan, Romuald Corbau, Donald S. Middleton, Charles E. Mowbray, Sandra D. Newman, Chris Phillips, Rob Webster & Mike Westby. (2011) Comparison of the Non‐Nucleoside Reverse Transcriptase Inhibitor Lersivirine with its Pyrazole and Imidazole Isomers. Chemical Biology & Drug Design 77:5, pages 393-397.
Crossref
Malcolm RowlandCarl Peck & Geoffrey Tucker. (2011) Physiologically-Based Pharmacokinetics in Drug Development and Regulatory Science. Annual Review of Pharmacology and Toxicology 51:1, pages 45-73.
Crossref
Angus N. R. Nedderman & Don K. Walker. 2011. Pharmacokinetics in Drug Development. Pharmacokinetics in Drug Development 131 143 .
Dirk Jochmans, Maria Anders, Inge Keuleers, Liesbeth Smeulders, Hans-Georg Kräusslich, Günter Kraus & Barbara Müller. (2010) Selective killing of human immunodeficiency virus infected cells by non-nucleoside reverse transcriptase inhibitor-induced activation of HIV protease. Retrovirology 7:1.
Crossref
Manoli Vourvahis, Michelle Gleave, Angus N. R. Nedderman, Ruth Hyland, Iain Gardner, Martin Howard, Sarah Kempshall, Claire Collins & Robert LaBadie. (2010) Excretion and Metabolism of Lersivirine (5-{[3,5-Diethyl-1-(2-hydroxyethyl)(3,5- 14 C 2 )-1 H -pyrazol-4-yl]oxy}benzene-1,3-dicarbonitrile), a Next-Generation Non-Nucleoside Reverse Transcriptase Inhibitor, after Administration of [ 14 C]Lersivirine to Healthy Volunteers . Drug Metabolism and Disposition 38:5, pages 789-800.
Crossref
Gerd Fätkenheuer, Schlomo Staszewski, Andreas Plettenburg, Frances Hackman, Gary Layton, Lynn McFadyen, John Davis & Tim M Jenkins. (2009) Activity, pharmacokinetics and safety of lersivirine (UK-453,061), a next-generation nonnucleoside reverse transcriptase inhibitor, during 7-day monotherapy in HIV-1-infected patients. AIDS 23:16, pages 2115-2122.
Crossref
Don Walker, Joe Brady, Deepak Dalvie, John Davis, Martin Dowty, J. Neil Duncan, Angus Nedderman, R. Scott Obach & Pat Wright. (2009) A Holistic Strategy for Characterizing the Safety of Metabolites through Drug Discovery and Development. Chemical Research in Toxicology 22:10, pages 1653-1662.
Crossref
Charles E. Mowbray, Catherine Burt, Romuald Corbau, Simon Gayton, Michael Hawes, Manos Perros, Isabelle Tran, David A. Price, Faye J. Quinton, Matthew D. Selby, Paul A. Stupple, Rob Webster & Anthony Wood. (2009) Pyrazole NNRTIs 4: Selection of UK-453,061 (lersivirine) as a Development Candidate. Bioorganic & Medicinal Chemistry Letters 19:20, pages 5857-5860.
Crossref
Charles E. Mowbray, Romuald Corbau, Michael Hawes, Lyn H. Jones, James E. Mills, Manos Perros, Matthew D. Selby, Paul A. Stupple, Rob Webster & Anthony Wood. (2009) Pyrazole NNRTIs 3: Optimisation of physicochemical properties. Bioorganic & Medicinal Chemistry Letters 19:19, pages 5603-5606.
Crossref
Masoud Jamei, David Turner, Jiansong Yang, Sibylle Neuhoff, Sebastian Polak, Amin Rostami-Hodjegan & Geoffrey Tucker. (2009) Population-Based Mechanistic Prediction of Oral Drug Absorption. The AAPS Journal 11:2, pages 225-237.
Crossref
Masoud Jamei, Gemma L. Dickinson & Amin Rostami-Hodjegan. (2009) A Framework for Assessing Inter-individual Variability in Pharmacokinetics Using Virtual Human Populations and Integrating General Knowledge of Physical Chemistry, Biology, Anatomy, Physiology and Genetics: A Tale of ‘Bottom-Up’ vs ‘Top-Down’ Recognition of Covariates. Drug Metabolism and Pharmacokinetics 24:1, pages 53-75.
Crossref

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Order Reprints Request Corporate Permissions

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

Request Academic Permissions

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.

Related research

People also read lists articles that other readers of this article have read.

Recommended articles lists articles that we recommend and is powered by our AI driven recommendation engine.

Cited by lists all citing articles based on Crossref citations.
Articles with the Crossref icon will open in a new tab.